Most cellular processes are carried out by multi-protein complexes. The identification and composition of such complexes is crucial for understanding how the ensemble of expressed proteins (The Proteome) is organized into functional units. The goal of the proposal is to establish a complete protein interaction map of the Drosophila melanogaster proteome based on the isolation and Mass spectrometric analysis of purified protein complexes associated with individually tagged proteins. This will determine the first complete metazoan proteome map beyond the level of binary protein interactions. The experimental system we propose to use offers an organism which has been extensively studied at a genetic and genomic level, has an established validity as a model for vertebrate biology, and offers the possibility of sophisticated genetic manipulations to determine cellular function.